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Biomedical subjects

G Zhao

Publications and source records attributed to G Zhao.

At least 91 records · Page 5Linked to original sources
PubMed2000

Analysis and prevention of failure causes of percutaneous implantable port for tumor chemotherapy.

The failure causes of percutaneous implantable port (PIP) for tumor chemotherapy were analyzed and the appropriate preventing measures were put forward. During Feb. 1995 to Feb. 1999, 10 patients with tumor undergoing failure insertion of PIP were retrospectively studied. We placed the PIP in the hepatic artery in 3 patients with liver carcinoma after operation, in the internal iliac artery in 5 patients with colonic or rectal carcinoma after operation and in the left gastric artery in 2 patients with stomach carcinoma after operation. The results showed that in the 10 patients, chemotherapeutic agent effusion around the PIP and local tissue necrosis in 5 cases, infection and abscess formation around the PIP in 3 cases, PIP body rupture in one case and the catheter sliding into the internal iliac artery occurred. It was concluded that taking measures during PIP insertion could prevent the occurrence of complications and is beneficial to the implementation of scheduled chemotherapeutic protocol for the patients.

Adult↗
PubMed2000

Allogeneic bone marrow transplantation with co-stimulatory blockade induces macrochimerism and tolerance without cytoreductive host treatment.

Allogeneic bone marrow transplantation (in immunocompetent adults) has always required cytoreductive treatment of recipients with irradiation or cytotoxic drugs to achieve lasting engraftment at levels detectable by non-PCR-based techniques ('macrochimerism' or 'mixed chimerism'). Only syngeneic marrow engraftment at such levels has been achieved in unconditioned hosts. This requirement for potentially toxic myelosuppressive host pre-conditioning has precluded the clinical use of allogeneic bone marrow transplantation for many indications other than malignancies, including tolerance induction. We demonstrate here that treatment of naive mice with a high dose of fully major histocompatibility complex-mismatched allogeneic bone marrow, followed by one injection each of monoclonal antibody against CD154 and cytotoxic T-lymphocyte antigen 4 immunoglobulin, resulted in multi-lineage hematopoietic macrochimerism (of about 15%) that persisted for up to 34 weeks. Long-term chimeras developed donor-specific tolerance (donor skin graft survival of more than 145 days) and demonstrated ongoing intrathymic deletion of donor-reactive T cells. A protocol of high-dose bone marrow transplantation and co-stimulatory blockade can thus achieve allogeneic bone marrow engraftment without cytoreduction or T-cell depletion of the host, and eliminates a principal barrier to the more widespread use of allogeneic bone marrow transplantation. Although efforts have been made to minimize host pre-treatment for allogeneic bone marrow transplantation for tolerance induction, so far none have succeeded in eliminating pre-treatment completely. Our demonstration that this can be achieved provides the rationale for a safe approach for inducing robust transplantation tolerance in large animals and humans.

Abatacept↗
PubMed2000

Endogenous nitric oxide in the control of skeletal muscle oxygen extraction during exercise.

Our previous studies uncovered an inhibitory effect of nitric oxide (NO) on leg skeletal muscle respiration in dogs at rest. The role of NO in the modulation of O2 consumption and O2 extraction in hindlimb muscle during elevated metabolic states was investigated in chronically instrumented dogs while walking and at three exercise intensities which markedly increased hindlimb blood flow. Walking resulted in increased O2 consumption by 17 +/- 4 mL min-1 and O2 extraction from 24 +/- 1 to 37 +/- 8%, with no alteration in hindlimb blood flow (BFLeg) and vascular resistance (VRLeg). Running at the highest speed (9.1 mph) resulted in an increase in BFLeg from 0.67 +/- 0.05 to 2.2 +/- 0.1 L min-1, a reduction of VRLeg and elevation of hindlimb O2 consumption from 33 +/- 3 to 226 +/- 21 mL min-1 and O2 extraction from 29 +/- 2 to 61 +/- 5%, with a decrease in leg venous PO2 from 38 +/- 1 to 25 +/- 1 mmHg. After nitro-L-arginine (NLA) (35 mg kg-1, i.v.) to inhibit endogenous NO synthesis, walking caused greater increases in hindlimb O2 consumption (29 +/- 5 mL min-1) and O2 extraction (43 +/- 1 to 60 +/- 3%) (both P < 0.05), with no significant change in BFLeg. During running at the highest speed, BFLeg was 1.9 +/- 0.1 L min-1 (P < 0. 05) and VRLeg was higher, accompanied by increases in hindlimb O2 consumption from 49 +/- 7 to 318 +/- 24 mL min-1 and O2 extraction from 41 +/- 2 to 79 +/- 4% (both P < 0.05), with a greater decrease in leg venous PO2 from 33 +/- 1 to 20 +/- 1 mmHg (P < 0.05). Similar results were found for intermediate levels of exercise. Our results indicate that NO modulates hindlimb skeletal muscle O2 extraction and O2 usage whether blood flow increased or not during exercise.

Acetylcholine↗
PubMed2000

A novel transmembrane serine/threonine protein kinase gene from a rifamycin SV-producing amycolatopsis mediterranei U32.

Genomic DNA sequencing in the vicinity of methylmalonyl-CoA mutase gene (mutAB) from a rifamycin SV-producing Amycolatopsis mediterranei U32 allowed us to clone, sequence, and identify a gene encoding a novel serine/threonine protein kinase (amk). The sequence contains a complete ORF of 1821 base pairs encoding a predicted protein of 606 amino acids in length. The N-terminal domain of the protein shows significant homology to the catalytic domain of other protein kinases from both prokaryotic and eukaryotic sources. It also contains all the structural features that are highly conserved in active protein kinases, including the Gly-X-Gly-X-X-Gly motif of ATP-binding and the essential amino acids known to be important for the recognition of the correct hydroxyamino acid in serine/threonine protein kinase. This protein kinase gene was expressed in Escherichia coli and was shown to have the ability of autophosphorylation. The autophosphorylated site was found to be the threonine at position 164 by labeled phosphoamino acid analysis and site-directed mutagenesis. The C-terminal half of protein kinase was found to contain strong transmembrane structures by PhoA fusion protein analysis, suggesting that Amk protein kinase is a transmembrane protein. A Southern hybridization experiment showed that this type of protein kinase is distributed ubiquitously and might play significant physiological roles in the various species of streptomycetes. However, overexpression of amk gene in Streptomyces cinnamonensis showed no effect on methylmalonyl-CoA mutase activity, monensin production and the hyphae morphology. Although its biological role is still unknown, Amk protein kinase is the first transmembrane serine/threonine protein kinase described for genus Amycolatopsis.

Actinomycetales↗
PubMed2000

Depolarization-associated iron release with abrupt reduction in pulmonary endothelial shear stress in situ.

This study evaluated the roles of endothelial cell membrane potential and reactive oxygen species (ROS) in the increase of tissue free iron during lung ischemia. Oxygenated ischemia was produced in the isolated rat lung by discontinuing perfusion while ventilation with O2 was maintained. We have shown previously that tissue oxygenation is maintained in this model of ischemia and that biochemical changes are the result of an abrupt reduction in endothelial shear stress. With 1 hr oxygenated ischemia, generation of ROS, evaluated by oxidation of dichlorodihydrofluorescein (H2DCF) to fluorescent dichlorofluorescein, increased 8.0-fold, lung thiobarbituric acid reactive substances (TBARS) increased 3.4-fold, and lung protein carbonyl content increased 2.4-fold. Lung tissue free iron, measured in the lung homogenate with a fluorescent desferrioxamine derivative, increased 4.0-fold during ischemia. Pretreatment of lungs with thapsigargin abolished the increase in free iron with ischemia indicating that this effect is dependent on Ca2+ release from intracellular stores. Perfusion of lungs with high (25 mM) K+ to depolarize the endothelium also led to a significant increase in tissue free iron. Pretreatment of lungs with 35 microM cromakalim, a K+-channel agonist, significantly inhibited both ischemia-induced tissue oxidant injury and the increase in free iron with ischemia or with high K+ perfusion. A similar increase in free iron was observed when lungs were ventilated with either O2 or N2 during the ischemic period or were pre-perfused with an inhibitor of ROS production (diphenyleneiodonium). These results indicate that ROS generation is not required for ischemia-mediated iron release. Thus, ROS generation and iron release with ischemia are independent although both are subsequent to endothelial cell membrane depolarization.

Animals↗
PubMed2000

Polyunsaturated fatty acids in the food chain in the United States.

In the United States, intake of n-3 fatty acids is approximately 1.6 g/d ( approximately 0.7% of energy), of which 1.4 g is alpha-linolenic acid (ALA; 18:3) and 0.1-0.2 g is eicosapentaenoic acid (EPA; 20:5) and docosahexaenoic acid (DHA; 22:6). The primary sources of ALA are vegetable oils, principally soybean and canola. The predominant sources of EPA and DHA are fish and fish oils. Intake data indicate that the ratio of n-6 to n-3 fatty acids is approximately 9.8:1. Food disappearance data between 1985 and 1994 indicate that the ratio of n-6 to n-3 fatty acids has decreased from 12.4:1 to 10.6:1. This reflects a change in the profile of vegetable oils consumed and, in particular, an approximate 5.5-fold increase in canola oil use. The ratio of n-6 to n-3 fatty acids is still much higher than that recommended (ie, 2.3:1). Lower ratios increase endogenous conversion of ALA to EPA and DHA. Attaining the proposed recommended combined EPA and DHA intake of 0.65 g/d will require an approximately 4-fold increase in fish consumption in the United States. Alternative strategies, such as food enrichment and the use of biotechnology to manipulate the EPA and DHA as well as ALA contents of the food supply, will become increasingly important in increasing n-3 fatty acid intake in the US population.

Adolescent↗
PubMed2000

Lowering dietary saturated fat and total fat reduces the oxidative susceptibility of LDL in healthy men and women.

The present study examined the effects of reducing dietary total fat and saturated fat (SFA) on LDL oxidative susceptibility in 27 healthy men and women (age 24-65 y). Each subject consumed each of three diets for 8 wk: an average American diet (AAD, 34% energy from fat, 15% from SFA), a Step-1 diet (29% fat, 9% SFA) and a very low SFA diet (Low-Sat, 25% fat, 6% SFA). In vitro LDL oxidation was assessed by copper-mediated oxidation, as measured by the kinetics of conjugated diene formation and lipid peroxide formation. Compared with the AAD, plasma LDL-cholesterol (LDL-C) and HDL cholesterol levels were 8% lower (P: = 0.16 and P: = 0.11, respectively), in subjects when they consumed the Step-1 diet and 11% (P: < 0.03) and 14% (P: < 0.057) lower, respectively, when they consumed the Low-Sat diet. Conjugated diene production and oxidation rate were 7% (P: < 0. 05) and 9% (P: < 0.05) lower, respectively. The reduction of lipid peroxide formation was 9% (P: < 0.05) in subjects when they consumed the Low-Sat diet vs. the AAD. In addition, lipid peroxide and conjugated diene formation were positively correlated with plasma total and LDL-C and apolipoprotein B (apo B) levels (r = 0.5-0.6, P: < 0.001), suggesting that quantity of LDL is an important determinant of oxidative modification. Furthermore, at the same level of apo B or LDL-C, LDL from subjects when they consumed either Step-1 or Low-Sat diets was less susceptible (P: < 0.05) to oxidation than those when they consumed the AAD, suggesting that qualitative changes also affect LDL oxidative susceptibility. Therefore, the benefits of lowering dietary SFA may extend beyond decreasing LDL-C levels and include favorable qualitative changes in LDL that further decrease risk of coronary heart disease.

Adult↗
PubMed2000

Identification and characterization of the penicillin-binding protein 2a of Streptococcus pneumoniae and its possible role in resistance to beta-lactam antibiotics.

To further understand the role of penicillin-binding protein 2a (PBP 2a) of Streptococcus pneumoniae in penicillin resistance, we confirmed the identity of the protein as PBP 2a. The PBP 2a protein migrated electrophoretically to a position corresponding to that of PBP 2x, PBP 2a, and PBP 2b of S. pneumoniae and was absent in a pbp2a insertional mutant of S. pneumoniae. We found that the affinities of PBP 2a for penicillins were lower than for cephalosporins and a carbapenem. When compared with other S. pneumoniae PBPs, PBP 2a exhibited lower affinities for beta-lactam antibiotics, especially penicillins. Therefore, PBP 2a is a low-affinity PBP for beta-lactam antibiotics in S. pneumoniae.

Bacterial Proteins↗
PubMed2000

Reduced NO-dependent arteriolar dilation during the development of cardiomyopathy.

Our previous studies have suggested that there is reduced nitric oxide (NO) production in canine coronary blood vessels after the development of pacing-induced heart failure. The goal of these studies was to determine whether flow-induced NO-mediated dilation is altered in coronary arterioles during the development of heart failure. Subepicardial coronary arterioles (basal diameter 80 microm) were isolated from normal canine hearts, from hearts with dysfunction but no heart failure, and from hearts with severe cardiac decompensation. Arterioles were perfused at increasing flow or administered agonists with no flow in vitro. In arterioles from normal hearts, flow increased arteriolar diameter, with one-half of the response being NO dependent and one-half prostaglandin dependent. Shear stress-induced dilation was eliminated by removing the endothelium. Arterioles from normal hearts and hearts with dysfunction but no failure responded to increasing shear stress with dilation that reached a maximum at a shear stress of 20 dyn/cm(2). In contrast, arterioles from failing hearts showed a reduced dilation, reaching only 55% of the dilation seen in vessels of normal hearts at a shear stress of 100 dyn/cm(2). This remaining dilation was eliminated by indomethacin, suggesting that the NO-dependent component was absent in coronary microvessels after the development of heart failure. Similarly, agonist-induced NO-dependent coronary arteriolar dilation was markedly attenuated after the development of heart failure. After the development of severe dilated cardiomyopathy and heart failure, the NO-dependent component of both shear stress- and agonist-induced arteriolar dilation is reduced or entirely absent.

Animals↗
PubMed2000

Depressed modulation of oxygen consumption by endogenous nitric oxide in cardiac muscle from diabetic dogs.

Our previous study indicated that nitric oxide (NO)-dependent coronary vasodilation was impaired in conscious dogs with diabetes. Our goal was to determine whether modulation of O(2) consumption by NO is depressed in canine cardiac muscle after diabetes. Diabetes was induced by injection of alloxan (40-60 mg/kg iv), dogs were killed after diabetes was induced (4-5 wk), and the cardiac muscle from the left ventricle was cut into 15- to 30-mg slices. O(2) uptake by the muscle slices was measured polarographically with a Clark-type O(2) electrode. S-nitroso-N-acetylpenicillamine decreased O(2) consumption in normal and diabetic tissues (10(-4) M, 61 +/- 7 vs. 61 +/- 8%, P > 0.05). Bradykinin (10(-4) M)- or carbachol (CCh, 10(-4) M)-induced inhibition of O(2) consumption was impaired in diabetic tissues (51 +/- 6 vs. 17 +/- 4% or 48 +/- 4 vs. 19 +/- 3%, respectively, both P < 0.05 compared with normal). The inhibition of O(2) consumption by kininogen or kallikrein was depressed in diabetic tissues as well. In coronary microvessels from diabetic dogs, bradykinin or ACh (10(-5) M) caused smaller increases in NO production than those from normal dogs. Our results indicate that the modulation of O(2) consumption by endogenous, but not exogenous, NO is depressed in cardiac muscle from diabetic dogs, most likely because of decreased release of NO from the vascular endothelium.

Acetylcholine↗
PubMed2000

Simvastatin upregulates coronary vascular endothelial nitric oxide production in conscious dogs.

Statin drugs can upregulate endothelial nitric oxide (NO) synthase (eNOS) in isolated endothelial cells independent of lipid-lowering effects. We investigated the effect of short-term simvastatin administration on coronary vascular eNOS and NO production in conscious dogs and canine tissues. Mongrel dogs were instrumented under general anesthesia to measure coronary blood flow (CBF). Simvastatin (20 mg. kg(-1). day(-1)) was administered orally for 2 wk; afterward, resting CBF was found to be higher compared with control (P < 0.05) and veratrine- (activator of reflex cholinergic NO-dependent coronary vasodilation) and ACh-mediated coronary vasodilation were enhanced (P < 0.05). Response to endothelium-independent vasodilators, adenosine and nitroglycerin, was not potentiated. After simvastatin administration, plasma nitrate and nitrite (NO(x)) levels increased from 5.22 +/- 1.2 to 7. 79 +/- 1.3 microM (P < 0.05); baseline and agonist-stimulated NO production in isolated coronary microvessels were augmented (P < 0.05); resting in vivo myocardial oxygen consumption (MVO(2)) decreased from 6.8 +/- 0.6 to 5.9 +/- 0.4 ml/min (P < 0.05); NO-dependent regulation of MVO(2) in response to NO agonists was augmented in isolated myocardial segments (P < 0.05); and eNOS protein increased 29% and eNOS mRNA decreased 50% in aortas and coronary vascular endothelium. Short-term administration of simvastatin in dogs increases coronary endothelial NO production to enhance NO-dependent coronary vasodilation and NO-mediated regulation of MVO(2).

Acetylcholine↗
PubMed2000

Anti-inflammatory effects of triptolide in human bronchial epithelial cells.

Triptolide (PG490, 97% pure) is a diterpenoid triepoxide with potent anti-inflammatory and immunosuppressive effects in transformed human bronchial epithelial cells and T cells (Qiu D, Zhao G, Aoki Y, Shi L, Uyei A, Nazarian S, Ng JC-H, and Kao PN. J Biol Chem 274: 13443-13450, 1999). Triptolide, with an IC(50) of approximately 20-50 ng/ml, inhibits normal and transformed human bronchial epithelial cell expression of interleukin (IL)-6 and IL-8 stimulated by phorbol 12-myristate 13-acetate (PMA), tumor necrosis factor-alpha, or IL-1 beta. Nuclear runoff and luciferase reporter gene assays demonstrate that triptolide inhibits IL-8 transcription. Triptolide also inhibits the transcriptional activation, but not the DNA binding, of nuclear factor-kappa B. A cDNA array and clustering algorithm analysis reveals that triptolide inhibits expression of the PMA-induced genes tumor necrosis factor-alpha, IL-8, macrophage inflammatory protein-2 alpha, intercellular adhesion molecule-1, integrin beta(6), vascular endothelial growth factor, granulocyte-macrophage colony-stimulating factor, GATA-3, fra-1, and NF45. Triptolide also inhibits constitutively expressed cell cycle regulators and survival genes cyclins D1, B1, and A1, cdc-25, bcl-x, and c-jun. Thus anti-inflammatory, antiproliferative, and proapoptotic properties of triptolide are associated with inhibition of nuclear factor-kappa B signaling and inhibition of genes known to regulate cell cycle progression and survival.

Algorithms↗
PubMed2000

Is there an optimal diet for the hypertriglyceridemic patient?

Many dietary factors affect plasma triglycerides. Those which decrease the triglyceride level include n-3 fatty acids from fish oil, weight loss, alcohol restriction, and a higher fat (unsaturated fat) diet, whereas a high-carbohydrate, low-fat diet increases triglycerides. The individual responses and the associated magnitude of change in triglycerides as a result of these different dietary factors will vary. For patients with hypertriglyceridemia, fish oil supplements will usually elicit the most potent effects. However, some patients can normalize their triglyceride level with weight loss plus exercise, by avoiding or limiting their alcohol intake, and by increasing the total fat content of their diet. In addition, fish oil supplements can help further to reduce plasma triglycerides. Thus, the combined effects of multiple dietary interventions provide the most potent means of maximally lowering the plasma triglyceride level.

Coronary Disease↗
PubMed2000

Targeted overexpression of insulin-like growth factor I to osteoblasts of transgenic mice: increased trabecular bone volume without increased osteoblast proliferation.

Insulin-like growth factor I (IGF-I) is an important growth factor for bone, yet the mechanisms that mediate its anabolic activity in the skeleton are poorly understood. To examine the effects of locally produced IGF-I in bone in vivo, we targeted expression IGF-I to osteoblasts of transgenic mice using a human osteocalcin promoter. The IGF-I transgene was expressed in bone osteoblasts in OC-IGF-I transgenic mice at high levels in the absence of any change in serum IGF-I levels, or of total body growth. Bone formation rate at the distal femur in 3-week-old OC-IGF-I transgenic mice was approximately twice that of controls. By 6 weeks, bone mineral density as measured by dual energy x-ray, and quantitative computed tomography was significantly greater in OC-IGF-I transgenic mice compared with controls. Histomorphometric measurements revealed a marked (30%) increase femoral cancellous bone volume in the OC-IGF-I transgenic mice, but no change in the total number of osteoblasts or osteoclasts. Transgenic mice also demonstrated an increase in the osteocyte lacunea occupancy, suggesting that IGF-I may extend the osteocyte life span. We conclude that IGF-I produced locally in bone osteoblasts exerts its anabolic effect primarily by increasing the activity of resident osteoblasts.

Animals↗
PubMed2000

Menopausal symptoms: experience of Chinese women.

OBJECTIVES: To investigate the prevalence of symptoms in middle-aged Chinese rural and city women of different occupations; and to explore the relationship between symptoms, hormone levels and other factors. METHODS: This cross-sectional study included 806 women aged 41-60 years, selected by multistage cluster sampling and a structured interview questionnaire. The response rate was 95%. The sample compromised 402 professional urban women and 404 women farmers living in rural areas. Some 209 women were randomly selected from the two groups for hormonal assay and bone mineral density screening. RESULTS: The professional group was more symptomatic than the farming group (p < 0.01). The presence of symptoms was significantly related to an increasing level of education. There were no significant differences between occupational groups in levels of estradiol follicle stimulating hormone (FSH) and luteinizing hormone (LH). Estradiol level and bone mineral density were decreased and FSH and LH increased in the postmenopausal group (p < 0.05) compared with the other menopausal groups. Hot flushes were the only symptom to be significantly associated with hormone levels (estradiol and LH). The occurrence of symptoms was significantly related to indications of bone and joint disease, heart disease, primary dysmenorrhea, decline in sexual interest, irregular menses and feelings of becoming older, sad and lost. These factors were all reported more often by the professional women than by the farmers. CONCLUSION: Symptom experience in mid-life Chinese women is related to both biological and psychosocial factors.

Adult↗
PubMed2000

Assessment of the bioavailability of rare earth elements in soils by chemical fractionation and multiple regression analysis.

The bioavailability of rare earth elements (REEs) in soils was evaluated, based on the combination of chemical fractionation and multiple regression analysis. REEs in soils were partitioned by a sequential extraction procedure into water soluble (F(ws)), exchangeable (F(ec)), bound to carbonates (F(cb)), bound to organic matter (F(om)), bound to Fe-Mn oxides (F(fm)) and residual (F(rd)) fractions. Alfalfa (Medicago Staiva Linn.) had been grown on the soils in a pot-culture experiment under greenhouse conditions for 35 days. The concentrations of REEs in fractions and plant were determined by inductively coupled plasma-mass spectrometry (ICP-MS). Chemical fractionation showed that (F(ws)) fraction of REEs was less than 0.1% and residual (F(rd)) was the dominant form, more than 60% in soils. Bioaccumulation of REEs was observed in Alfalfa. REE availability to the plant was evaluated by multiple regression analysis. F(ws), F(ec), F(cb) and F(om) fractions were significantly correlated with REE uptake by alfalfa. But the exchangeable Pr(F(ec)) was significantly correlated with Pr concentration in alfalfa. F(ec), F(cb) and F(om) greatly contributed to La and Nd bioavailability; F(ec) and F(om) to Ce, Gd and Dy; F(ec) and F(cb) to Yb; and F(ws), F(ec) and F(om) to total REEs. This meant that the bioavailability of different species of REEs varied with individual REE. The results of this study indicated that the sequential extraction procedure, in conjunction with multiple regression analysis, may be useful for the prediction of plant uptake of REEs from soils.

Biological Availability↗